{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:51:44Z","timestamp":1740171104752,"version":"3.37.3"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T00:00:00Z","timestamp":1507075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","award":["RFA 48.07"],"award-info":[{"award-number":["RFA 48.07"]}],"id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital myopathies due to ryanodine receptor (<jats:italic><jats:styled-content style=\"fixed-case\">RYR<\/jats:styled-content>1<\/jats:italic>) mutations are increasingly identified and correlate with a wide range of phenotypes, most commonly that of malignant hyperthermia susceptibility and central cores on muscle biopsy with rare reports of distal muscle weakness, but in the setting of early onset global weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a case of a patient presenting with childhood onset hand stiffness and adult onset progressive hand weakness and jaw contractures discovered to have two variants in the <jats:italic><jats:styled-content style=\"fixed-case\">RYR<\/jats:styled-content>1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient manifested with distal upper limb weakness which progressed to involve the distal lower limb, proximal upper limb, as well as the face in addition to limited jaw opening. Creatine kinase was mildly elevated with <jats:styled-content style=\"fixed-case\">EMG<\/jats:styled-content> findings supporting a myopathy. Muscle biopsy showed features consistent with centronuclear myopathy. Whole exome sequencing revealed a novel heterozygous pathogenic variant in <jats:italic><jats:styled-content style=\"fixed-case\">RYR<\/jats:styled-content>1<\/jats:italic> (c.12315_12328del<jats:styled-content style=\"fixed-case\">AGAAATCCAGTTCC<\/jats:styled-content>, p.Glu4106Alafs*8), and a heterozygous missense variant (c.10648C&gt;T, p.Arg3550Trp) of unknown significance in compound heterozygous state.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We expand the spectrum of <jats:italic><jats:styled-content style=\"fixed-case\">RYR<\/jats:styled-content>1<\/jats:italic>\u2010related myopathy with the description of a novel phenotype in an adult patient presenting with hand weakness and suggest considering <jats:italic><jats:styled-content style=\"fixed-case\">RYR<\/jats:styled-content>1<\/jats:italic> analysis in the diagnosis of distal myopathies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.338","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T01:56:37Z","timestamp":1507168597000},"page":"800-804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<i>RYR1<\/i> causing distal myopathy"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-5824","authenticated-orcid":false,"given":"Ruple S.","family":"Laughlin","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Wieben","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Milone","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2010.01149.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21278"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10231"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl071"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00134.2016"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.2.284"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000188870.37076.f2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.01.016"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2016.06.001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22056"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.05.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20696"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0993-51"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00037-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg244"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12713"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-013-0434-4"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2016.07.018"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22119"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl221"}],"container-title":["Molecular Genetics &amp; 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